АУТОИММУННЫЕ ЗАБОЛЕВАНИЯ НЕРВНОЙ СИСТЕМЫ: СОСТОЯНИЕ ПРОБЛЕМЫ И ПЕРСПЕКТИВЫ

This review highlights the achievements in the field of autoimmune diseases of the nervous system over the last 15 years. It became possible to deepen the understanding of medical and social significance of these diseases, form the concept of nosologic unit heterogeneity, describe new and atypical forms of demyelinating diseases of the central and peripheral nervous system, autoimmune diseases of the neuromuscular synapse. Also, it is important to mention, that the new antigens were identified, the diagnostic panel of autoantibodies was developed and put into practice. Furthermore, the clinical practice guidelines for the diagnosis and management of patients were developed, the new drugs were tested and included in these guidelines. The scientists of the biggest Russian neurological centre, Research Centre of Neurology (Moscow), developed a vaccine for immunotherapy of multiple sclerosis, studied pathomorphosis of Guillain–Barre syndrome, specified the components of its pathogenesis, improved the programs of pathogenetic therapy, which led to the decrease in mortality from 30 to 3%, helped to decrease the AVL period by 2 times, hasten the recovery of independent walking by 2.5 times. Nowadays different biomarkers of diseases of the central and peripheral nervous system are studied and modern technologies in neurorehabilitation are applied. В статье освещены достигнутые за последние 15 лет результаты в области аутоиммунных заболеваний нервной системы: укрепилось понимание медико-социальной значимости этих болезней, сформировалась концепция гетерогенности нозологических единиц, описаны новые и атипичные формы демиелинизирующих заболеваний центральной и периферической нервной системы, аутоиммунных болезней нервно-мышечного синапса. Идентифицированы новые антигены, разработаны и внедрены в практику диагностические панели аутоантител. Сформулированы клинические рекомендации по диагностике и ведению, апробированы и включены в стандарты новые лекарственные препараты. В крупнейшем неврологическом центре России, Научном центре неврологии (Москва), разработана вакцина для иммунотерапии рассеянного склероза, исследуются биомаркеры болезней центральной и периферической нервной системы, внедряются современные технологии реабилитации. Приоритетными достижениями являются изучение патоморфоза синдрома Гийена–Барре, детализация звеньев патогенеза, совершенствование программы патогенетической терапии, позволившей снизить летальность с 30 до 3%, сократить в 2 раза сроки пребывания на искусственной вентиляции легких и в 2,5 раза ― сроки восстановления самостоятельной ходьбы.

Motor Cortex Hyperexcitability, Neuroplasticity, and Degeneration in Amyotrophic Lateral Sclerosis

Neuronal hyperexcitability is a well-known phenomenon in amyotrophic lateral sclerosis and other neurodegenerative diseases. The use of transcranial magnetic stimulation in clinical and research practice has recently made it possible to detect motor cortex hyperexcitability under clinical conditions. Despite numerous studies, the mechanisms and sequelae of the development of hyperexcitability still have not been completely elucidated. In this chapter, we discuss the possibilities for detecting motor cortex hyperexcitability in patients with amyotrophic lateral sclerosis using transcranial magnetic stimulation. The potential relationship between hyperexcitability and neuronal degeneration or neuroplasticity processes is discussed using the data obtained by navigated transcranial magnetic stimulation and neuroimaging data, as well as the data of experimental studies

Increased motor cortex excitability during motor imagery in brain-computer interface trained subjects

Background: Motor imagery (MI) is the mental performance of movement without muscle activity. It is generally accepted that MI and motor performance have similar physiological mechanisms. Purpose: To investigate the activity and excitability of cortical motor areas during MI in subjects who were previously trained with an MI-based brain-computer interface (BCI). Subjects and Methods: Eleven healthy volunteers without neurological impairments (mean age, 36 years; range: 24–68 years) were either trained with an MI-based BCI (BCI-trained, n = 5) or received no BCI training (n = 6, controls). Subjects imagined grasping in a blocked paradigm task with alternating rest and task periods. For evaluating the activity and excitability of cortical motor areas we used functional MRI and navigated transcranial magnetic stimulation (nTMS). Results: fMRI revealed activation in Brodmann areas 3 and 6, the cerebellum, and the thalamus during MI in all subjects. The primary motor cortex was activated only in BCI-trained subjects. The associative zones of activation were larger in non-trained subjects. During MI, motor evoked potentials recorded from two of the three targeted muscles were significantly higher only in BCI-trained subjects. The motor threshold decreased (median = 17%) during MI, which was also observed only in BCI-trained subjects. Conclusion: Previous BCI training increased motor cortex excitability during MI. These data may help to improve BCI applications, including rehabilitation of patients with cerebral palsy.Web of Science7art. no. 0016

РАСЧЕТ ДЛИНЫ И ШИРИНЫ РАСКРЫТИЯ ТРЕЩИНЫ, РАЗВИВАЮЩЕЙСЯ ВО ВРЕМЕНИ

The executed investigations make it possible to calculate crack’s length and opening development in the concrete elements.Выполненные исследования дают возможность проводить расчет длины и ширины раскрытия трещины в железобетонных элементах

Sequence analysis of the non-coding control region of John Cunningham virus isolates from patients with multiple sclerosis treated with natalizumab

Introduction. The John Cunningham virus (JCPyV) causes a fatal demyelinating disease of the central nervous system known as progressive multifocal leukoencephalopathy (PML). In healthy people, the JCPyV non-coding control region (NCCR) is not rearranged, while NCCRs in immunocompromised patients are characterized by frequent rearrangements and can be associated with PML development. Therefore, patients treated with natalizumab, which decreases the migration of leukocytes and monocytes through the blood-brain barrier to inflammatory foci, are at increased risk of developing PML. The purpose of the study was to analyze NCCR sequences of JCPyV isolates from patients with multiple sclerosis (MS) treated with natalizumab. Materials and methods. A total of 26 blood plasma samples and 8 cerebrospinal fluid samples were analyzed using nested PCR to study the JCPyV NCCR structure in Russian MS patients treated with natalizumab. The NCCRs present in the samples were cloned and sequenced by Sanger sequencing. All the JCPyV NCCR sequences were compared with the archetype sequence and mapped. The NCCR sequences were also examined for presence of putative transcription factor binding sites. Results. A total of 48 NCCR sequences were found. The analysis showed that up to 55% of NCCRs were identified as rearranged NCCRs, while the other were archetype-like NCCRs. All the sequences can be divided into 6 types with one dominant rearrangement pattern. This rearranged NCCR was also found in a patient with the confirmed PML diagnosis and a poor prognosis. All the rearranged NCCRs were characterized by the presence of additional transcription factor binding sites. Conclusion. The study has helped identify previously unknown NCCR patterns typical of MS patients treated with natalizumab in Russia, thus confirming the need for the further research on NCCR rearrangements in MS patients undergoing natalizumab treatment to gain better understanding of the origin of neurovirulent JCPyV variants

Theta-gamma phase-amplitude coupling: physiological basics, analysis methods, and perspectives of translation into clinical practice

Studying rhythmic neural synchronization (cross-frequency coupling in various ranges) is an emerging topic in present-day neurophysiology. One of the best-studied cross-frequency couplings is theta-gamma phase-amplitude coupling that contributes to the cognitive function and may vary in patients with several conditions associated with cognitive impairment. Changes in theta-gamma coupling can be registered in a wide range of diseases associated with cognitive decline. The review covers the physiological basics of theta-gamma coupling, its registration and calculation, correlation with cognitive test results in healthy volunteers, and changes in patients. We have discussed the results of the preliminary studies of frequency-dependent non-invasive brain stimulation based on theta-gamma coupling

Безопасность транскраниальной магнитной стимуляции: обзор международных рекомендаций и новые данные

Transcranial magnetic stimulation (TMS) is a rapidly developing method of neuromodulation. The use of TMS has increased significantly in both research and clinical practice. This allows not only to better understand this method, but also assess possible risks and consequences for both healthy individuals and patients. In 1998 and 2009 safety, ethical considerations, and application guidelines for the use of TMS in clinical practice and research were published. These recommendations are now the basis for safe application of the method in clinical practice and research. Safety of brain stimulation includes several aspects: the prevention and treatment of adverse effects, the strategy of patient and stimulation protocols selection, as well as safety and monitoring procedures. The most common adverse effects of TMS include headache and neck pain, syncope, transient hearing impairment. The risk of epileptic seizureis extremely low and can be minimized by careful selection of patients and the use of safe stimulation protocols. Careful selection of patients is important, taking into account a large number of factors that influence the risk of adverse effects. These factors are considered in the questionnaires to identify limitations and absolute or relative contraindications to TMS. Another important part of TMS safety is the choice of the stimulation protocol and parameters such as intensity, frequency, duration of one train of stimuli, and the interstimulus interval. Currently, the recommended limits of stimulation parameters are covered in the safety guidelines. It is also necessary to follow the procedure, including the monitoring the patient's condition during TMS and the providing qualified assistance in case of adverse effects.Транскраниальная магнитная стимуляция (ТМС) – активно развивающийся метод нейромодуляции. В последние годы значительно увеличилась частота применения ТМС как в исследовательской, так и в клинической практике, что постоянно открывает новые возможности метода, позволяет оценивать риски и последствия как для здоровых лиц, так и для пациентов с болезнями нервной системы. В 1998 и 2009 гг. были опубликованы рекомендации международной группы экспертов по безопасности и этическими аспектами ТМС, которые и сегодня остаются основной инструкцией по использованию данного метода в исследовательской и клинической практике.  Безопасность процедуры стимуляции мозга – многоуровневая задача, включающая профилактику и устранение нежелательных эффектов, стратегию отбора пациентов и протоколов стимуляции, а также обеспечение безопасности и мониторинга состояния пациента во время процедуры. К распространенным нежелательным эффектам ТМС относятся боль в шее и головная боль, синкопе, преходящие изменения слуха. По данным литературы, риск провокации эпилептического приступа крайне низок и минимизирован при тщательном отборе пациентов и использовании безопасных протоколов стимуляции. При планировании процедуры ТМС значение имеет отбор пациентов с учетом большого числа факторов риска нежелательных эффектов, а также абсолютных и относительных противопоказаний проведения стимуляции. На этом этапе перед проведением ТМС рекомендуется использовать специальные опросники. Следующим важным вопросом безопасности ТМС является протокол стимуляции с подбором таких параметров, как интенсивность, частота, продолжительность одной серии стимулов и межстимульный интервал. Сегодня максимально допустимые значения перечисленных параметров регламентированы в рекомендациях по безопасности, а их изменение допускается только в клинических исследованиях. Для обеспечения безопасности необходимо соблюдение ряда организационных мер, в том числе мониторинг состояния пациента во время процедуры и возможность оказания квалифицированной помощи при развитии нежелательных явлений. 

Hypertensive crisis as cerebrovascular disease risk factor

Objective. To assess main epidemiological indicators for hypertensive crises (HC) in the population of productive age and to study possible correlations of crisis associated arterial hypertension (AH) with clinical and instrumental phenomenon of chronic cerebrovascular diseases. Materials and methods. Data of several studies presented: cross-sectional studies of 726 people aged 35-64 and 415 people aged 40-59. Observational cohort study of 109 patients aged 57.4±5.8 with uncomplicated AH. For the detection of HC in anamnesis, there were used special criteria which widens standard HC definition for additional account of light and mild severity cases. Results. Overall AH prevalence was 45% (95% CI 41-51), in men - 48% (40.2-55.9), in women - 45% (38.4-51.6). History of HC in anamnesis was 11.8% (95% CI 9-15.2), in men 8.8% (5.4-14) and in women - 13.8% (10-18.7). Proportion of HC associated AH defined at the level of 25-30% of all AH cases. The most prevalence of HC associated AH was found in people with “high normal” (130-139/85-89) arterial pressure - 37%. Prevalence of the complaints on headaches, dizziness, poor memory and lower intellectual productivity was higher in people with HC. Chronic cerebrovascular disease was found 2-fold frequently in HC associated AH. But in generally analysis of possible correlations of HC with clinical and instrumental phenomenon of chronic cerebrovascular diseases didn’t revealed any statistically significant differences. Conclusion. HC burden for healthcare system is serious, because it is important risk factor for cerebrovascular diseases and associated with significant lowering of the quality of life. Prevalence of the HC cases with light and mild severity is underestimated. Despite that the study of the most prevalent forms of HC (rare, light and mild severity) didn’t find any associations with morphological or persistent clinical pathology, functional phenomenon were found statistically significant frequently

Особенности течения СГБ в России: анализ 186 случаев

The medical records of 186 patients diagnosed with Guillain-Barré syndrome (GBS) who had been followed up at the Research Center of Neurology, Russian Academy of Medical Sciences, in 2000 to 2011 were retrospectively analyzed. Most (65 %) of the patients had severe GBS; 19 % of the patients were on mechanical ventilation (MV) for an average of 21 (13; 48) days. The forms of GBS, such as acute inflammatory demyelinating polyneuropathy (AIDP) (n = 141; 78 %), and axonal variants, such as acute motor axonal neuropathy (AMAN), acute sensorimotor axonal neuropathy (AMSAN), i. e. AMAN / AMSAN (n = 39; 22 %), were studied separately. There was a significant difference in the seasonal revalence (p < 0.05). AIDP was encountered evenly throughout the year; AMAN / AMSAN occurred in 46 % of cases in summer. AIDP was followed by acute respiratory viral infection in 35 % of cases; diarrhea wasby the axonal forms in 36 % (p < 0.05). The axonal forms ran a severer course than AIDP: MV was performed twice more frequently (33 and 15 %, respectively); its duration was 6‑fold longer: 90 (46; 102) and 15 (10; 21) days (p < 0.05). AMAN / AMSAN was characterized by a severer neurological status and disability in the acute period, as shown by the NIS, MRCss, INCAT, R-ODS, and Barthel scales; these patients showed a poorer response to pathogenetic therapy (p < 0.05): 59 % with an insufficient effect; 15 % of those with AIDP. After six years, the majority (84 %) of the patients with AIDP walked alone and only 16 % were assisted. In the same period, less than half of the patients (40 %) with AMAN / AMSAN walked alone and a third (29 %) could move with assistance and almost the same percentage (31 %) could not walk.Thus, a number of specific features of GBS were found in a Russian population (equal age and sex distribution; a larger percentage of the axonal forms than in European countries and the United States); however, the most characteristics did not differ from the global data.Проведен ретроспективный анализ медицинской документации 186 пациентов с установленным диагнозом синдрома Гийена – Барре (СГБ), наблюдавшихся в ФГБУ «Научный центр неврологии» РАМН в период с 2000 по 2011 г. У большинства пациентов (65 %) наблюдалось тяжелое течение СГБ, искусственная вентиляция легких (ИВЛ) проводилась 19 % больным продолжительностью в среднем 21 (13; 48) день.Были отдельно изучены формы СГБ: острая воспалительная демиелинизирующая полинейропатия (ОВДП) (n = 141; 78 %) и аксональные – острая моторная аксональная невропатия (ОМАН), острая моторно-сенсорная аксональная невропатия (ОМ-САН), т. е. ОМАН / ОМСАН (n = 39; 22 %). Выявлена существенная разница в сезонности (р < 0,05): ОВДП встречалась равномерно в течение всего года, ОМАН / ОМСАН в 46 % случаев возникали летом. В 35 % случаев ОВДП предшествовала острая респираторная вирусная инфекция, аксональным формам – диарея (36 %) (p < 0,05). Последние протекали достоверно тяжелее ОВДП: ИВЛ проводилась в 2 раза чаще (33 и 15 % соответственно), ее продолжительность была в 6 раз больше: 90 (46; 102) и 15 (10; 21) сут (p < 0,05). При ОМАН / ОМСАН достоверно тяжелее неврологический статус и инвалидизация в остром периоде по шкалам NIS, MRCss, INCAT, R-ODS и Бартела, эти пациенты хуже отвечают на патогенетическую терапию (р < 0,05): 59 % с недостаточным эффектом, по сравнению с 15 % при ОВДП. Через полгода большинство пациентов с ОВДП (84 %) ходили самостоятельно и только 16 % передвигались с поддержкой. При ОМАН / ОМСАН в эти же сроки менее половины пациентов ходили самостоятельно (40 %), треть могли передвигаться с поддержкой (29 %) и почти столько же (31 %) оставались обездвижены. Таким образом, выявлен ряд особенностей СГБ в российской популяции (распределение пациентов по возрасту и полу одинаковое, бо́льшая доля аксональных форм по сравнению со странами Европы и Америки), однако большинство характеристик не отличаются от мировых данных